Laryngeal cancer is a very aggressive tumor, the prognosis of which largely depends on the stage of the tumor at the time of the initial diagnosis. Over the past twenty years, High-throughput biological technologies let people begin to predict the result of the tumor by detecting the expression of genes and microRNAs. Dysregulated miRNAs were proved to play a significant role in oncogenesis and tumor progression by acting either as cancer suppressor or proto-oncogenes. Autophagy is a really important biological phenomenon. In some models, cancer may stimulate the occurrence of autophagy to maintain the function of mitochondrial and energy balance. Therefore, inhibiting the process of autophagy could be beneficial for cancer treatment. A great number of studies have shown that microRNAs can inhibit the development of various cancer by regulating the process of autophagy[12–14]. However, up to now, there has been no systematic method to identify Autophagy-associated microRNAs in LSCC. Therefore, it is necessary to find a way to screen AAMRs and explore their roles in the occurrence and development of LSCC.
In our study, we intersect the candidate AAMRs screened from two datasets (TCGA and GSE124679) to investigate the prognosis of AAMRs. According to the result of the Cox regression analysis, we identified 6 key AAMRs. Based on the result of multivariate step Cox regression, we constructed a new risk index model divided LSCC patients into high-risk group and low-risk group. It is found that the survival result of LSCC is better in low-risk group and risk index could independently related to the prognosis of LSCC. Our study does not support the correlation between risk index and clinical feature of LSCC, which does not meet our expectations. We suspect that this may be related to the deletion of some samples with incomplete clinical information when we included LSCC samples.
Among 6 key AAMRs (hsa-miR-100-5p, hsa-miR-143-3p, hsa-miR-3607-5p, hsa-miR-454-3p, hsa-miR-455-5p, hsa-miR-99a-5p) identified by our studies, most of them have been shown to regulate autophagy in various cancer cells[15–19]. However, only a few studies have explored the relationship between microRNAs and autophagy in LSCC. In recent research, Chen et. al. reported that miR-101 can inhibit autophagy, proliferation through targeting EZH2 in LSCC. Wang et.al. indicated that miR-26b may inhibit the development of LSCC via autophagy by regulating PTEN/AKT pathway. Anyway, microRNA may play an important role in regulating autophagy and affecting the development of LSCC. Our research provides new ideas and targets for further exploration of this neighborhood. Specifically, all 6 key AAMRs were enriched in the mTOR signaling pathway, which plays a vital role in the regulation of cell growth, survival and autophagy. mTOR protein could function as a sensor of energy and nutrient levels, thus further negatively regulated the occurrence of autophagy. The research showed that inhibition of mTOR can significantly affect the proliferation and apoptosis in laryngeal cancer cell lines. Our result indicates that AAMRs may affect the development of LSCC through autophagy and mTOR signaling pathways.
Our study dose has some limitations. Firstly, the data source for our analysis was based on TCGA and GEO database, thus making it impossible to obtain all patient information. Secondly,
GSE124679 dataset does not offer the clinical information of LSCC samples, therefore, the new prognostic model needs to be validated by other independent studies. Thirdly, more experiments are needed to validate the role of AAMRs in the autophagy process of laryngeal cancer cells.